The purpose of the study is to assess the safety of the addition of sitagliptin, and its effect on hemoglobin A1c (A1C) in pediatric participants 10-17 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control. The primary hypothesis for this study is that sitagliptin reduces A1C more than placebo after 20 weeks of treatment.

100 mg oral tablet of sitagliptin prior to the morning meal in Phase A and Phase B.

Other Name: Januvia

Drug: Placebo to sitagliptin

After randomization: Participants randomized to the Placebo Phase A/Metformin Phase B arm will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. Phase B: Participants in the Placebo Phase A/Metformin Phase B arm will continue to receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. For 1 week, participants will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal.

Drug: Placebo to metformin

After randomization: Participants randomized to the Sitagliptin Arm and those randomized to the Placebo Phase A/Metformin Phase B arm will receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. Phase B: Participants in the Sitagliptin Arm will continue to receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. For 1 week participants will receive oral tablets of placebo to metformin (500 mg), 2 tablets prior to the morning and evening meals.

Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 2 (open-label), participants receiving sitagliptin, placebo or metformin will receive insulin according to routine clinical practice. For participants on background insulin therapy, insulin doses can be up-titrated for Rescue Step 2; the change in insulin dose will be at the discretion of the investigator.

Biological: Insulin

Stable doses of background insulin will be sourced locally and administered subcutaneously based on instructions provided by the Investigator (based on accepted local, national or international guidelines).

Active Comparator: Metformin

Metformin (500 mg) oral tablets, 2 tablets twice daily prior to morning and evening meals and placebo to sitagliptin (100 mg), oral tablet once daily for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will continue to receive Phase A treatment for 34 weeks (Phase B). This arm of the study was removed by a protocol amendment.

Drug: Metformin

Metformin (500 mg), 2 tablets twice daily prior to morning and evening meals (dose will be up-titrated starting at 500 mg/day and increased by 500 mg weekly increments up to a total daily dose of 1000 mg twice daily).

Other Name: Glucophage

Drug: Placebo to sitagliptin

After randomization: Participants randomized to the Placebo Phase A/Metformin Phase B arm will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. Phase B: Participants in the Placebo Phase A/Metformin Phase B arm will continue to receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. For 1 week, participants will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal.

Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 2 (open-label), participants receiving sitagliptin, placebo or metformin will receive insulin according to routine clinical practice. For participants on background insulin therapy, insulin doses can be up-titrated for Rescue Step 2; the change in insulin dose will be at the discretion of the investigator.

Experimental: Placebo Phase A/Sitagliptin Phase B

Placebo to sitagliptin oral tablet once a day and placebo to metformin oral tablets (500 mg), 2 tablets twice daily prior to morning and evening meals for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will receive 1 tablet of sitagliptin daily and 2 tablets of metformin placebo twice daily prior to morning and evening meals (Phase B). This arm of the study was removed by a protocol amendment.

Drug: Sitagliptin

100 mg oral tablet of sitagliptin prior to the morning meal in Phase A and Phase B.

Other Name: Januvia

Drug: Placebo to sitagliptin

After randomization: Participants randomized to the Placebo Phase A/Metformin Phase B arm will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. Phase B: Participants in the Placebo Phase A/Metformin Phase B arm will continue to receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. For 1 week, participants will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal.

Drug: Placebo to metformin

After randomization: Participants randomized to the Sitagliptin Arm and those randomized to the Placebo Phase A/Metformin Phase B arm will receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. Phase B: Participants in the Sitagliptin Arm will continue to receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. For 1 week participants will receive oral tablets of placebo to metformin (500 mg), 2 tablets prior to the morning and evening meals.

Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 2 (open-label), participants receiving sitagliptin, placebo or metformin will receive insulin according to routine clinical practice. For participants on background insulin therapy, insulin doses can be up-titrated for Rescue Step 2; the change in insulin dose will be at the discretion of the investigator.

Metformin (500 mg), 2 tablets twice daily prior to morning and evening meals (dose will be up-titrated starting at 500 mg/day and increased by 500 mg weekly increments up to a total daily dose of 1000 mg twice daily).

Other Name: Glucophage

Drug: Placebo to sitagliptin

After randomization: Participants randomized to the Placebo Phase A/Metformin Phase B arm will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. Phase B: Participants in the Placebo Phase A/Metformin Phase B arm will continue to receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. For 1 week, participants will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal.

Drug: Placebo to metformin

After randomization: Participants randomized to the Sitagliptin Arm and those randomized to the Placebo Phase A/Metformin Phase B arm will receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. Phase B: Participants in the Sitagliptin Arm will continue to receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. For 1 week participants will receive oral tablets of placebo to metformin (500 mg), 2 tablets prior to the morning and evening meals.

Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 2 (open-label), participants receiving sitagliptin, placebo or metformin will receive insulin according to routine clinical practice. For participants on background insulin therapy, insulin doses can be up-titrated for Rescue Step 2; the change in insulin dose will be at the discretion of the investigator.

Biological: Insulin

Stable doses of background insulin will be sourced locally and administered subcutaneously based on instructions provided by the Investigator (based on accepted local, national or international guidelines).

Detailed Description:

This trial is of approximately 56 weeks in duration, including a screening period of up to 1 week, a 1-week single-blind placebo run-in period, a 20-week placebo-controlled, double blind treatment period [Phase A] and a 34-week double-blind active controlled treatment period [Phase B] during which participants randomized to the placebo arm who have not initiated glycemic rescue therapy with metformin during Phase A will receive metformin (in a blinded manner). A telephone contact will be performed 14 days after the last dose of study medication to assess for any serious adverse events (SAEs).

Two arms of the study were removed from the study by a protocol amendment.

Eligibility

Ages Eligible for Study:

10 Years to 17 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Type 2 Diabetes Mellitus (T2DM)

Has not received treatment with an oral antihyperglycemic agent (AHA) for ≥12 weeks prior to the Screening Visit/Visit 1, or is on a stable dose of insulin (without any other AHA) for at least 12 weeks prior to the Screening Visit/Visit 1.

An A1C of ≥6.5% and ≤10.0% (For participants on insulin: an A1C ≥7.0% and ≤10.0%).

Hypersensitivity or contraindication (according to the product circular in the country of the investigational site) to metformin.

Chronic treatment with a medication known to cause weight gain within 30 days of study start or weight loss or increased blood glucose within 8 weeks of study start or treated with an anti-psychotic within the past 12 weeks.

On a weight loss program and not in the maintenance phase or have undergone bariatric surgery within 12 months prior to study start.

On or likely to require treatment with ≥14 consecutive days or repeated courses of pharmacologic doses of corticosteroids.

Undergone a surgical procedure within the prior 4 weeks or has major surgery planned during the study.

History of congenital heart disease or cardiovascular disease other than hypertension.

Exhibits abnormal growth patterns or is being treated with growth hormone.

History of malignancy or clinically important hematologic disorder.

History of idiopathic acute pancreatitis or chronic pancreatitis.

Known history of recreational or illicit drug use, or of alcohol abuse or dependence (within the past year).

Donated blood products or has had phlebotomy of >10% of estimated total blood volume within 8 weeks of signing informed consent, or intends to donate blood products or receive blood products within the projected duration of the study.

Pregnant, has a positive urine pregnancy test at Screening Visit/Visit 1, is expecting to conceive within the projected duration of the study, or is breast-feeding.

Exclusionary laboratory values.

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485614